Content developed by Marie Fuzzati (IRCCS Mondino Foundation and France Parkinson) and Ludivine Breger (INSERM), in close collaboration with MIUR. For more information or for questions, please contact experimentalmodels@jpnd.eu.

General Information

Corresponding human genotype: R1441G is an autosomal dominant missense mutation in the ROC domain of the LRRK2 gene. It is very common in familial cases of Parkinson’s disease and has a near complete penetrance.

Transgene expression

3-6 months: transgene expression is observed in the cortex, cerebellum, striatum and ventral midbrain with a 5-10 fold increase compared to endogenous LRRK2

Neurodegeneration

9-10 months: no loss of TH-positive neurons is observed in SN and VTA but a significant decrease in the average cell body size and the number of TH-positive dendrites are observed. TH striatal optical density is normal but spheroid and dystrophic neurites are present

Dopamine Homeostasis

9-10 months: Impaired DA release is detected in the striatum

Inclusions

Not reported. However, a significant increase in phosphorylated tau protein is observed in the brain of the transgenic mice (9-10 months)

Motor Behaviours

Up to 21 months: Contradictory results have been reported. Loss of rearing is observed in the cylinder test (6-12 months) as well as hypokinesia that progresses to apparent immobility (akinesia) between 10-12 months. However, according to other studies, only mild deficits in motor behaviours are observed up to 21 months, with some coordination impairments starting at 16 months (pole test, rotarod).

Electrophysiology

Not reported

Neuroinflammation

9-10, 16 months: no gliosis is observed

The EU Joint Programme – Neurodegenerative Disease Research (JPND) is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases, in particular Alzheimer’s. Learn More